A sleep bruxism detection system based on sensors in a splint - pilot clinical data.

It is difficult in a dental setting to accurately diagnose sleep bruxism and to objectively assess the severity, frequency or natural history of the condition in an individual patient. Yet this information is essential for the management of sleep bruxism and to plan appropriate dental treatment. The objective of this study was to clinically test a device that could be used to record bruxism events in a home environment. Pressure sensors were developed for use under the surface of an occlusal splint, and circuitry was designed to facilitate the recording and wireless transmission of the pressure sensor signal to a computer. Controlled mandibular movements were carried out in vivo to simulate bruxism and non-bruxism patterns. These patterns of force application were graphically presented to two examiners who were asked to identify the type of activity represented by the force curves. Examiners were largely able to distinguish bruxism from non-bruxism activity; the sensitivity ranged from 80% to 100% and the specificity from 75% to 100%. Using sensors in an occlusal splint, it is possible to recognise the typical tooth contact patterns seen in sleep bruxism. Such a device may be useful for monitoring sleep bruxism over an extended period at home.

Margin width is not predictive of residual disease on re-excision in breast conserving therapy.

BACKGROUND: There is lack of consensus regarding re-excision in breast-conserving therapy (BCT) and close margins. We hypothesize that margin width does not predict residual disease. METHODS: The cancer registry was queried from 2003 to 2008 for patients with BCT who underwent re-excision for <2-mm margins. Factors associated with additional disease were evaluated. RESULTS: One thousand eight hundred forty-three patients underwent BCT. Our re-excision rate was 42%. Clinicopathologic factors from 228 patients were analyzed. One hundred five patients (46%) had additional disease; of those, 58% had BCT and 42% mastectomy. One hundred twenty-three (54%) had no additional disease; of those 82% had BCT and 18% mastectomy. Of the 66 patients who underwent mastectomy, 44 (67%) had residual disease; of the 161 who had BCT, 61 (38%) had residual disease (P < 0.01). On univariate analysis, margin width did not correlate with residual disease. Multifocality, non-invasive histology, increasing number of close margins, and higher grade predicted additional disease (P < 0.05). On multivariate analysis, only number of close margins remained significant. CONCLUSIONS: Margin width does not predict additional disease. This challenges the practice of using this to select re-excision candidates. Our data suggest that tumor behavior and extent of disease, defined by volume of residual disease and invasiveness of histology, play a more significant role.

Optimal computed tomography-based biomarkers for prediction of incisional hernia formation.

PURPOSE: Unstructured data are an untapped source for surgical prediction. Modern image analysis and machine learning (ML) can harness unstructured data in medical imaging. Incisional hernia (IH) is a pervasive surgical disease, well-suited for prediction using image analysis. Our objective was to identify optimal biomarkers (OBMs) from preoperative abdominopelvic computed tomography (CT) imaging which are most predictive of IH development. METHODS: Two hundred and twelve rigorously matched colorectal surgery patients at our institution were included. Preoperative abdominopelvic CT scans were segmented to derive linear, volumetric, intensity-based, and textural features. These features were analyzed to find a small subset of OBMs, which are maximally predictive of IH. Three ML classifiers (Ensemble Boosting, Random Forest, SVM) trained on these OBMs were used for prediction of IH. RESULTS: Altogether, 279 features were extracted from each CT scan. The most predictive OBMs found were: (1) abdominopelvic visceral adipose tissue (VAT) volume, normalized for height; (2) abdominopelvic skeletal muscle tissue volume, normalized for height; and (3) pelvic VAT volume to pelvic outer aspect of body wall skeletal musculature (OAM) volume ratio. Among ML prediction models, Ensemble Boosting produced the best performance with an AUC of 0.85, accuracy of 0.83, sensitivity of 0.86, and specificity of 0.81. CONCLUSION: These OBMs suggest increased intra-abdominopelvic volume/pressure as the salient pathophysiologic driver and likely mechanism for IH formation. ML models using these OBMs are highly predictive for IH development. The next generation of surgical prediction will maximize the utility of unstructured data using advanced image analysis and ML.

Subacute ruminal acidosis reduces sperm quality in beef bulls.

Breeding bulls are commonly fed high-energy diets, which may induce subacute ruminal acidosis (SARA). In this experiment, 8 Santa Gertrudis bulls (age 20 ± 6 mo) were used to evaluate the extent and duration of effects of SARA on semen quality and the associated changes in circulating hormones and metabolites. The bulls were relocated and fed in yards with unrestricted access to hay and daily individual concentrate feeding for 125 d before SARA challenge. Semen was collected and assessed at 14-d intervals before the challenge to ensure acclimatization and the attainment of a stable spermiogram. The challenge treatments consisted of either a single oral dose of oligofructose (OFF; 6.5 g/kg BW) or an equivalent sham dose of water (Control). Locomotion, behavior, respiratory rate, and cardiovascular and gastrointestinal function were intensively monitored during the 24-h challenge period. Rumen fluid samples were retained for VFA, ammonia, and lactate analysis. After the challenge, semen was then collected every third day for a period of 7 wk and then once weekly until 12 wk, with associated blood collection for FSH, testosterone, inhibin, and cortisol assay. Percent normal sperm decreased in bulls dosed with OFF after the challenge period ( < 0.05) and continued to remain lower on completion of the study at 88 d after challenge. There was a corresponding increase in sperm defects commencing from 16 d after challenge. These included proximal cytoplasmic droplets ( < 0.001), distal reflex midpieces ( = 0.01), and vacuole and teratoid heads ( < 0.001). Changes in semen quality after challenge were associated with lower serum testosterone ( < 0.001) and FSH ( < 0.05). Serum cortisol in OFF bulls tended to be greater ( = 0.07) at 7 d after challenge. This study shows that SARA challenge causes a reduction in sperm quality sufficient to preclude bulls from sale as single sire breeding animals 3 mo after the event occurred.

Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer.

Oncolytic viral therapy is a promising new method of cancer treatment. Peritoneal dissemination of cancer is a common and fatal clinical condition seen in many malignancies, with few effective therapies available. G207, a multimutated replication-competent herpes simplex virus type-1, effectively treats disseminated peritoneal cancer. This study evaluates viral proliferation and subsequent tumoricidal effects in vitro and in vivo after regional viral delivery. In vitro studies demonstrate that G207 efficiently kills five human gastric cancer cell lines, and that permissiveness to viral replication is correlated with cytotoxicity. In a murine xenograft model of human gastric carcinomatosis, peritoneal delivery of G207 effectively kills tumor and prolongs survival. Data from quantitative PCR characterizes peritoneal clearance of virus after intraperitoneal injection, and identifies G207 replication within tumor cells in vivo, similar to in vitro proliferation. Further analysis of various organs confirms that G207 does not replicate within normal tissue after peritoneal delivery. Wild-type KOS viral replication was also demonstrated in vivo, with significant toxicity secondary to dissemination and encephalitis. In vivo viral proliferation of G207 is restricted to tumor cells, is correlated with in vitro assays, and is an important mechanism of anticancer efficacy.

Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy.

Herpes simplex viruses (HSV) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. They are natural human pathogens and the majority of adults have anti-HSV immunity. The current study examined the effect of preexisting immunity on the response to herpes-based oncolytic viral treatment of hepatic metastatic cancer in a murine model designed to simulate a clinical approach likely to be utilized for nonneurological tumors. Specifically, the anticancer effects of NV1020 or G207, two multimutated HSV-1 oncolytic viruses, were tested in immunocompetent mice previously immunized with a wild-type herpes simplex type 1 virus. Mice were documented to have humoral as well as cell-mediated immunity to HSV-1. Tumor response to oncolytic therapy was not measurably abrogated by immunity to HSV at the doses tested. The influence of route of viral administration was also tested in models of regional hepatic arterial and intravenous therapy. Route of viral administration influenced efficacy, as virus delivered intravenously produced some detectable attenuation while hepatic arterial therapy remained unaffected. These results demonstrate that when given at appropriate doses and in reasonable proximity to tumor targets, HSV-based oncolytic therapy can still be expected to be effective treatment for patients with hepatic malignancies.

Use of the ganciclovir implant for treating cytomegalovirus retinitis secondary to immunosuppression after bone marrow transplantation.

PURPOSE: To report a case in which we treated cytomegalovirus retinitis using an intravitreal ganciclovir sustained-release device in a patient negative for the human immunodeficiency virus, with a history of myeloproliferative syndrome with myelofibrosis and profound immunosuppression after allogeneic bone marrow transplantation. METHODS: Case report. Review of medical records and fundus photographs. RESULTS: After the ganciclovir device was implanted, the cytomegalovirus retinitis did not progress, and visual acuity improved. We removed the device 9 months after implantation. CONCLUSIONS: The ganciclovir sustained-release device may be useful for treating cytomegalovirus retinitis in patients without the acquired immunodeficiency syndrome who are profoundly immunosuppressed and fail conventional intravenous therapy. If immune suppression is of limited duration, the device can be removed.

Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses.

Pancreatic cancer is an aggressive, rapidly fatal disease against which current nonsurgical therapy has minimal impact. This study evaluates the efficacy of two novel, replication-competent, multimutated herpes viruses (G207 and NV1020) in an experimental model of pancreatic cancer. Four human pancreatic carcinoma cell lines were exposed to G207 or NV1020, and cell survival and viral progeny production were determined. Flank tumors in athymic mice were subjected to single or multiple injections of 1 x 10(7) G207 or NV1020, and tumor volume was evaluated over time. For all of the cell lines, G207 and NV1020 produced infection, viral replication, and cell lysis (P < 0.05). NV1020 resulted in a higher production of viral progeny compared to G207. The efficacy of viral tumor cell kill was greatest in those cells with the shortest in vitro doubling time. For flank tumors derived from hs766t, single or multiple injections of both viruses were equally effective and significantly reduced flank tumor burden (P < 0.05). Complete hs766t flank tumor eradication was achieved in 25% (5 of 20) of animals treated with G207 and 40% (8 of 20) of animals treated with NV1020. In vivo efficacy correlated with in vivo tumor doubling time. There were no adverse effects related to viral administration observed in any animal. NV1020 and G207 effectively infect and kill human pancreatic cancer cells in vitro and in vivo. Given the lack of effective nonoperative treatments for pancreatic cancer, oncolytic herpes viruses should be considered for clinical evaluation.

Establishing a prognosis for fire damaged sheep.

Twenty, mixed age merino sheep suffering moderate bushfire burns were placed under observation to monitor the effects of the damage and to determine what indicators would provide a prognosis for burnt sheep. Eight sheep died within 29 days of the fire from the effects of their burns, while one which was killed when unable to stand 45 days after the fire had a heavy internal parasite burden. The best indicators that an animal would not survive were immobility and recumbency associated with burns to the hooves and legs below the carpal and tarsal joints which caused swelling and a dry leathery appearance of the skin. Neither burns to the legs not associated with swelling, nor burns to the hooves, head and woolless areas were themselves critical; such affected sheep generally recovered without complication. It was considered that burnt sheep should be assessed daily for the first 10 days. Control of internal parasites and blowflies may be required for recovering groups of sheep. It was found that sheep which survived their burns did not become unthrifty.

The use of pneumatic retinopexy to delay surgical repair of a retinal detachment associated with the ganciclovir intraocular device.

Rhegmatogenous retinal detachments are associated with cytomegalovirus (CMV) retinitis and the use of the ganciclovir intraocular device. Pars plana vitrectomy with silicone oil tamponade is the preferred technique to repair such detachments. The authors describe the use of pneumatic retinopexy as part of a treatment strategy in the management of multiple retinal detachments in a patient with CMV retinitis treated with ganciclovir implants. Pneumatic retinopexy may benefit patients when the causative retinal break is superior and is located in an area of retina uninvolved with CMV infection, because it can be used to delay surgical intervention.

Dose-dependent improvements in outcome with adenoviral expression of interleukin-10 in a murine model of multisystem organ failure.

Targeted expression of interleukin-10 (IL-10) has been proposed as a means to suppress acute and chronic inflammation. We explored the capacity of targeted adenoviral expression of human or viral IL-10 to improve outcome in a zymosan-induced model of acute lung injury and multisystem organ failure. Intratracheal administration of adenovirus expressing either human or viral IL-10 prior to zymosan administration significantly improved survival at a dose of 10(7) particles (P<0.01), whereas the same recombinant vectors were ineffective at 10(8) particles and increased mortality at 10(9) particles. Improved survival after administration of 10(7) particles of adenovirus expressing viral or human IL-10 was associated with local tissue expression of IL-10 (100-300 pg/g wet wt). In contrast, mortality after administration of 10(9) particles was associated with markedly elevated IL-10 expression, both in the lung (10000-70000 pg/g wet wt) and systemically (1000-3000 pg/ml plasma), with evidence of an exaggerated systemic inflammatory response (plasma IL-6 and TNFalpha). Targeted gene expression of IL-10 can be used to treat acute inflammatory processes, but increased doses resulting in its systemic release are not associated with improvements in outcome, and may actually exacerbate acute inflammatory processes.

Modelling the impact testing of prescription lenses.

Lenses are tested in an impact test in which a steel ball is dropped from a height onto the centre of the lens. This causes the lens to deform until the stress in the lens reaches a point at which fracture occurs. A survey of the literature was carried out and analytical models of the load/deflection and of the deflection/stress relationships were selected. A mathematical model of the impact test on lenses was developed. This model consisted of calculating the load-deflection relationship of a lens loaded at a central point, combined with calculating the deflection at which fracture occurred. From this model the impact energy required to deform a lens to fracture was obtained. This was held to be equal to the minimum kinetic energy of an impactor, less losses, that would be needed to cause lens fracture. As the losses are small, the calculated energy was used as an estimate of the impact strength of the lens. These values were then compared to those established by experiment. The impact energies predicted by the model were a close approximation of the experimental results for the lenses tested.